Initiation of Adjuvant Therapy Within 3 Weeks After Surgical Resection of GBM Could Be Detrimental

Early initiation of chemoradiation after surgical resection of glioblastoma before 3 weeks may be detrimental to patients, while short delays beyond 5 weeks did not negatively impact the examined outcomes, according to a recent study published in Cancer.

The results suggested a detrimental impact on overall survival for early initiation that was consistent across each recursive partitioning analysis group.

“The absence of an effect on survival with a prolonged time interval suggests that a short delay in the initiation of chemoradiation beyond the traditional 4 to 5 weeks may not negatively affect overall survival in patients with glioblastoma and should be considered if clinically indicated without undue concern,” wrote the researchers. “Conversely, the current study also demonstrated a modest detriment in overall survival with early initiation of adjuvant therapy, defined as within 3 weeks from surgery.”

For multivariate analysis, there was no point after week 5 that was associated with a statistically significant change in overall survival for patients across all 3 classes. Meanwhile, weeks 0 to 1 (hazard ratio [HR], 1.18; 95% CI, 1.02-1.36), >1 to 2 (HR, 1.23; 95% CI, 1.16-1.31), and >2 to 3 (HR, 1.11; 95% CI, 1.07-1.15) showed a slightly worse overall survival (P< .03).

The researchers included 30,414 patients with glioblastoma from the National Cancer Database who underwent surgery and chemoradiation from 2004 to 2013. The recursive partitioning analysis were divided into 3 classes (III, IV, V) and included 5,250, 20,855, and 4309 patients, respectively.

“The current study demonstrates no clear survival detriment with delays beyond 5 weeks from surgery,” wrote the researchers. “In addition, the results indicate that there may be an overall survival detriment with the initiation of adjuvant therapy before 3 weeks from surgery. These results persisted across the recursive partitioning analysis classes, supporting that these outcomes are not driven solely by selection bias of patients with disparate prognoses.”

A significant limitation of the study was the lack of patients in the National Cancer Database with known MGMTstatus, precluding further analysis. Future studies should examine this variable in its research when possible.

More, the National Cancer Database lacked data on progression-free survival and local control endpoints, which are clinically relevant to the study. Further, the recursive partitioning analysis classifications used is an “extrapolation from the original definition.” Any conclusions drawn from this research should be interpreted within this context.

“This study is not advocating for delaying treatment as a new standard of care,” wrote the researchers. “However, these data, taken in the context of other supporting literature, favor avoiding the initiation of adjuvant therapy within the first 3 weeks after surgery if possible and could be used to reassure patients and providers in the scenario of unexpected delays, such as with postoperative complications or the wait times for molecular biomarker testing needed for clinical trial enrollment and other clinical decision making.”

Reference:

Press RH, Shafer SL, Jiang R, et al. Optimal Timing of Chemoradiotherapy After Surgical Resection of Glioblastoma: Stratification by Validated Prognostic Classification. Cancer. DOI: 10.1002/cncr.32797.